N-phenylbutanamide

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Ethylaniline was protected as 2-ethylacetanilide according to Method A2a, Step 1. The acetamide was converted to 2-ethyl-4-nitroaniline, then deprotected according to Method A2a, Step 2. The aniline was converted to 2-ethyl-4-nitrophenyl isothiocyanate according to Method A2a, Step 3. 1-Hydroxymethylcyclopentanamine was prepared according to Method B1c. The 2-hydroxyethylamine was converted to 1-chloromethylcyclopentanamine HCl salt according to Method B7e. 1-Chloromethylcyclopentanamine HCl salt was reacted with 2-ethyl-4-nitrophenyl isothiocyanate according to Method C1e to give 2-(2-ethyl-4-nitrophenylphenylimino)-3-thia-1-azaspiro[4.4]nonane. The thiazolidine was reacted with cyclopentyl bromide according to Method D2b to give 2-(2-ethyl-4-nitrophenylphenylimino)-1-cyclopentyl-3-thia-1-azaspiro[4.4]nonane.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Ethylaniline was protected as 2-ethylacetanilide according to Method A2a, Step 1. The acetamide was converted to 2-ethyl-4-nitroaniline, then deprotected according to Method A2a, Step 2. The aniline was converted to 2-ethyl-4-nitrophenyl isothiocyanate according to Method A2a, Step 3. 1-Hydroxymethylcyclopentanamine was prepared according to Method B1c. The 2-hydroxyethylamine was converted to 1-chloromethylcyclopentanamine HCl salt according to Method B7e. 1-Chloromethylcyclopentanamine HCl salt was reacted with 2-ethyl-4-nitrophenyl isothiocyanate according to Method C1e to give 2-(2-ethyl-4-nitrophenylphenylimino)-3-thia-1-azaspiro[4.4]nonane. The thiazolidine was reacted with cyclopentyl bromide according to Method D2b to give 2-(2-ethyl-4-nitrophenylphenylimino)-1-cyclopentyl-3-thia-1-azaspiro[4.4]nonane.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Ethylaniline was protected as 2-ethylacetanilide according to Method A2a, Step 1. The acetamide was converted to 2-ethyl-4-nitroaniline, then deprotected according to Method A2a, Step 2. The aniline was converted to 2-ethyl-4-nitrophenyl isothiocyanate according to Method A2a, Step 3. 1-Hydroxymethylcyclopentanamine was prepared according to Method B1c. The 2-hydroxyethylamine was converted to 1-chloromethylcyclopentanamine HCl salt according to Method B7e. 1-Chloromethylcyclopentanamine HCl salt was reacted with 2-ethyl-4-nitrophenyl isothiocyanate according to Method C1e to give 2-(2-ethyl-4-nitrophenylphenylimino)-3-thia-1-azaspiro[4.4]nonane. The thiazolidine was reacted with cyclopentyl bromide according to Method D2b to give 2-(2-ethyl-4-nitrophenylphenylimino)-1-cyclopentyl-3-thia-1-azaspiro[4.4]nonane.

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: First, 16 g of aniline, 200 mL of tetrahydrofuran (THF), 26 g of triethylamine (Et3N) were put in a 500 mL three-neck flask, and stirred under cooling in ice. Then, a mixed solution of 18 g of btyryl chloride and 50 mL of THF was dripped to the above mixed solution through a 100 mL dropping funnel. After the dripping, the mixture was stirred for 2 hours while the temperature was increased to room temperature. After the stirring, the reaction mixture was added to 200 mL of water, and stirred at room temperature. This mixed solution was separated to an organic layer and an aqueous layer, and the aqueous layer was extracted with chloroform. The extract and the previously resulting organic layer were combined, and washed with saturated saline. After the washing, anhydrate magnesium sulfate was added to the organic layer for drying. The mixture after the drying was subjected to gravity filtration, and the filtrate was concentrated to give a solid. This solid was washed with a mixed solvent of chloroform and hexane, so that N-phenylbutyramide was prepared (a white solid, yield: 92%). The synthetic scheme of Step 1 is shown by (a-7). under cooling in ice After the dripping, the mixture was stirred for 2 hours while the temperature stirred at room temperature This mixed solution was separated to an organic layer an aqueous layer, and the aqueous layer was extracted with chloroform The extract washed with saturated saline After the washing, anhydrate magnesium sulfate was added to the organic layer for drying The mixture after the drying was subjected to gravity filtration the filtrate was concentrated to give a solid This solid was washed with a mixed solvent of chloroform and hexane, so that N-phenylbutyramide was prepared (a white solid, yield: 92%)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Using 2-ethylacetanilide (4.9 g) and iodobenzene (12.4 ml), a reaction as made in the same manner as in 1) of Production Example 2. The subsequent purification by silica gel column chromatography (developing solvent, ethyl acetate:hexane=1:3) produced 2-ethyl-N-phenylacetanilide (4.0 g; yield, 56%) as a brown oil. a reaction The subsequent purification by silica gel column chromatography (developing solvent, ethyl acetate:hexane=1:3)

Conditions: temp:2.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Ethylaniline (82.6 mmol, 10 gams) was taken in round bottom flask equipped with a liquid addition funnel and a guard tube. Triethylamine (165 mmol, 16.69 grams) was added to it in one lot. The mass, thus obtained, was cooled to 0-5° C. and added acetyl chloride (123 mmol, 9.73 grams) drop wise, while maintaining the mass temperature below 10° C. After addition of acetyl chloride, cooling was removed and reaction was stirred at 25-28° C. for a period of 3 hours. After completion of the reaction, the reaction mixture was poured onto 200 mL of ice water and aqueous layer was extracted with dichloromethane (2×100 mL). The combined dichloromethane extracts were then washed with water, brine and dried over anhydrous magnesium sulfate. The volatiles were removed under the reduced pressure to obtain 14.09 grams of compound. equipped with a liquid addition funnel and a guard tube The mass, thus obtained while maintaining the mass temperature below 10° C cooling was removed reaction After completion of the reaction was extracted with dichloromethane (2×100 mL) The combined dichloromethane extracts were then washed with water, brine dried over anhydrous magnesium sulfate The volatiles were removed under the reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Ethylaniline was protected as 2-ethylacetanilide according to Method A2a, Step 1. The acetamide was converted to 2-ethyl-4-nitroaniline, then deprotected according to Method A2a, Step 2. The aniline was converted to 2-ethyl-4-nitrophenyl isothiocyanate according to Method A2a, Step 3. 1-Hydroxymethylcyclopentanamine was prepared according to Method B1c. The 2-hydroxyethylamine was converted to 1-chloromethylcyclopentanamine HCl salt according to Method B7e. 1-Chloromethylcyclopentanamine HCl salt was reacted with 2-ethyl-4-nitrophenyl isothiocyanate according to Method C1e to give 2-(2-ethyl-4-nitrophenylphenylimino)-3-thia-1-azaspiro[4.4]nonane. The thiazolidine was reacted with cyclopentyl bromide according to Method D2b to give 2-(2-ethyl-4-nitrophenylphenylimino)-1-cyclopentyl-3-thia-1-azaspiro[4.4]nonane.